A First in Human Single and Multiple Ascending Dose and Open Label Food Effect Study of OR-101 in Healthy Subjects

NCT ID: NCT06045624

Last Updated: 2024-04-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-17
• Study Completion Date: 2024-02-06

Brief Summary

This first in human phase 1 study to Study will evaluate safety, tolerability, and pharmacokinetics of Single Ascending dose (SAD), Food effect (FE) and Multiple ascending dose (MAD) of OR-101 Administered Orally in healthy subjects

Detailed Description

There are three phases of the study: Single ascending dose (SAD), food effect (FE), and multiple ascending dose (MAD) phases.

In the SAD and MAD Phases, up to 64 subjects in each phase may be enrolled in the study. Fortyeight subjects will be randomised in the initial six cohorts; upto 16 subjects may be enrolled in two additional cohorts. For each dose cohort a total of 8 subjects (6 receiving OR-101 and 2 placebo) will be enrolled and randomized.

In the FE phase, up to 8 subjects who will receive a high fat meal prior to administration of OR101 may be enrolled in the study. Subjects who discontinue prior to completion may be replaced at the discretion of the Sponsor and the Investigator.

The SRC including the Investigator, Medical Monitor, Study Director as well as other ad hoc representatives as appropriate will regularly monitor all aspects of subject safety throughout this study. The SRC will review all available, cumulative safety and PK data in a blinded manner to assess the safety of each dose level of OR-101 prior to escalating to the next dose level.

Conditions

Alopecia Areata

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A

Drug- OR-101

Dosage level: SAD participants will receive either placebo or one of planned doses levels of 15mg, 45mg, 150mg, 450mg, 900mg, 1500mg OR-101 in dose escalating manner in cohorts 1-6.

Dosage form: Solution

Route of administration- Oral

Group Type: EXPERIMENTAL

OR-101 (Single ascending dose)

Intervention Type: DRUG

SAD participants will receive either placebo or one of planned doses levels of 15mg, 45mg, 150mg, 450mg, 900mg, 1500mg OR-101 in dose escalating manner in cohorts 1-6.

Part B

Drug- OR101

Dosage level: Food effect participants (8 subjects in 9 cohorts) will only receive OR-101with a high fat meal prior to administration and subjects in corresponding dose under fasted condition will serve as their reference group.

Dosage form: Solution

Route of administration- Oral

Group Type: EXPERIMENTAL

OR-101 (Food effect)

Intervention Type: DRUG

Food effect participants (8 subjects in 9 cohorts) will only receive OR-101with a high fat meal prior to administration and subjects in corresponding dose under fasted condition will serve as their reference group

Part C

Drug- OR-101

Dosage level: MAD participants will receive either placebo or one of planned doses levels of 15mg, 45mg, 135mg, 270mg, 540mg and 900mg OR-101 in dose escalating manner in cohorts 1-6. Total dosage of cohort 7 and 8 will be decided based on Safety review committe's input where cohort 8 will receive this daily for 7 days.

Dosage form: Solution

Route of administration- Oral

Group Type: EXPERIMENTAL

OR-101 (Multiple ascending dose)

Intervention Type: DRUG

MAD participants will receive either placebo or one of planned doses levels of 15mg, 45mg, 135mg, 270mg, 540mg and 900mg OR-101 in dose escalating manner in cohorts 1-6. Total dosage of cohort 7 and 8 will be decided based on Safety review committe's input where cohort 8 will receive this daily for 7 days

Placebo

Placebo comparators taken by participants randomised to the placebo arm across Part A and C of the study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo across Part A and C of the study

Interventions

OR-101 (Single ascending dose)

SAD participants will receive either placebo or one of planned doses levels of 15mg, 45mg, 150mg, 450mg, 900mg, 1500mg OR-101 in dose escalating manner in cohorts 1-6.

Intervention Type: DRUG

OR-101 (Food effect)

Food effect participants (8 subjects in 9 cohorts) will only receive OR-101with a high fat meal prior to administration and subjects in corresponding dose under fasted condition will serve as their reference group

Intervention Type: DRUG

OR-101 (Multiple ascending dose)

MAD participants will receive either placebo or one of planned doses levels of 15mg, 45mg, 135mg, 270mg, 540mg and 900mg OR-101 in dose escalating manner in cohorts 1-6. Total dosage of cohort 7 and 8 will be decided based on Safety review committe's input where cohort 8 will receive this daily for 7 days

Intervention Type: DRUG

Placebo

Participants will receive matching placebo across Part A and C of the study

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Is willing to sign and date IRB-approved ICF.

2. Is a man or woman between the ages of 18 and 55, inclusive.

3. Has a BMI of 18.0 to 30.5 kg/m2 and a total body weight >50 kg for a man and >45 kg for a woman at Screening and Check-in of Day -1.

4. Is in good health as determined by medical history, PE, clinical laboratory studies, ECGs, VS, and Investigator's judgement (repeat tests are allowed at PI's discretion).

5. Is willing to minimize sun exposure, avoid phototherapy, and not to use tanning beds, tanning booths, or sun lamps during the study (Day 1 to EOS).

6. If a woman of childbearing potential, must not be pregnant, lactating, or planning to become pregnant during the study.

7. Willing to follow the methods of contraception as per the protocol.

Exclusion Criteria

1. Has any condition that precludes a subject's ability to comply with study requirements, including completion of the study visits.

2. Has a history or current evidence of a clinically significant cardiovascular, respiratory, endocrine, gastrointestinal, renal, hepatic, hematologic, immunologic, genitourinary, dermatological, psychiatric or neurologic abnormality or disease or other medical disorder, including cancer or malignancies.

3. Has clinically significant abnormal laboratory test values as determined by the Investigator or the local or Sponsor Medical Monitor.

4. has BP and HR measurement after 5 minutes rest in a supine position of:

• systolic BP >150 or <90 mmHg
• diastolic BP of >95 or <45 mmHg
• HR >100 or <50 bpm
• 2 repeats of the subject's BP or HR are permitted for eligibility purposes

5. Has a history of, or currently has, any clinically significant ECG finding, or a QT interval corrected by Fridericia's method (QTcF) of > 450 msec for males and > 470 msec for females.

6. Has unacceptable COVID-19 test results (if required per site policy at the time of enrollment).

7. Has a history of HIV, or hepatitis B or C, or positive serology. Note: Subjects with a history of hepatitis C who have been treated and cured (no detectable HCV RNA) are allowed.

8. Has a history of tuberculosis.

9. Has an active immune suppressed condition or disease.

10. Has a history of recurrent HSV infections (HSV 1 and/or 2) requiring chronic antiviral suppressive therapies (defined as greater than 4 episodes or breakout per calendar year).

11. Is unable to swallow study drug or has a known intolerance or hypersensitivity to OR-101 or any of the excipients contained in the study drug.

12. Has participated in a clinical study and received active treatment during the last 30 days or 5 half-lives, whichever is longer, prior to Day 1.

13. Has received any prescription medication within the last 14 days prior to Day 1 or nonprescription OTC medication within the last 7 days prior to Day 1, or supplement (e.g., St John's wort, echinacea, kava kava, and common valerian) that may induce/inhibit CYP isozymes within the last 30 days or 5 half-lives, whichever is longer, prior to Day 1.

Note: acetaminophen (paracetamol) or ibuprofen are permitted medications on an as needed basis.

14. Has recent history (within 6 months of screening) of alcohol or drug abuse.

15. Consumes more than 14 units of alcohol per week (7 days) for at last 30 days prior to Day 1 and throughout the end of the study or those who have a history of alcohol or drug/chemical abuse Note: 1 unit of alcohol is equivalent to 240 mL of beer, 120 mL of wine, or 30 mL of spirits.

16. Consumes greater than 500 mg of caffeine or xanthine-containing products per day (e.g., approximately five 240-mL cups of coffee, ten 240-mL cups of tea, twelve 360-mL cans of soft drinks, energy drinks) for at last 30 days prior to Day 1 and throughout the end of the study.

17. Is an active smoker and/or has used nicotine or nicotine-containing products (e.g., nicotine patch and electronic cigarette) within 3 months of Day 1 (to be confirmed by carbon monoxide breath test).

18. Refuses to abstain from alcohol, grapefruit, or Seville-orange containing foods (e.g., orange marmalade) or beverages, from 48 hours prior to Day 1 through the end of the study.

19. Has donated blood > 500 mL within 60 days prior to the Screening Visit (Plasma donation is allowed).

20. Is an employee of Ornovi Pty Ltd or the CRO, or has an immediate family member who is an employee of Ornovi Pty Ltd or the CRO.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ornovi, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

SCIENTIA Clinical Research Ltd

Randwick, New South Wales, Australia

Countries

Australia

Other Identifiers

OR101-HS101

Identifier Type: -

Identifier Source: org_study_id